生物学最新文献_第10页

KPNA3 regulates histone locus body formation by modulating condensation and nuclear import of NPAT.

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2025-01-06 Epub Date: 2024-12-02 DOI: 10.1083/jcb.202401036

Shui Bo Xu, Xiu Kui Gao, Hao Di Liang, Xiao Xia Cong, Xu Qi Chen, Wen Kai Zou, Jia Li Tao, Zhao Yuan Pan, Jiao Zhao, Man Huang, Zhang Bao, Yi Ting Zhou, Li Ling Zheng

{"title":"KPNA3 regulates histone locus body formation by modulating condensation and nuclear import of NPAT.","authors":"Shui Bo Xu, Xiu Kui Gao, Hao Di Liang, Xiao Xia Cong, Xu Qi Chen, Wen Kai Zou, Jia Li Tao, Zhao Yuan Pan, Jiao Zhao, Man Huang, Zhang Bao, Yi Ting Zhou, Li Ling Zheng","doi":"10.1083/jcb.202401036","DOIUrl":"10.1083/jcb.202401036","url":null,"abstract":"The histone locus body (HLB) is a membraneless organelle that determines the transcription of replication-dependent histones. However, the mechanisms underlying the appropriate formation of the HLB in the nucleus but not in the cytoplasm remain unknown. HLB formation is dependent on the scaffold protein NPAT. We identify KPNA3 as a specific importin that drives the nuclear import of NPAT by binding to the nuclear localization signal (NLS) sequence. NPAT undergoes phase separation, which is inhibited by KPNA3-mediated impairment of self-association. In this, a C-terminal self-interaction facilitator (C-SIF) motif, proximal to the NLS, binds the middle 431-1,030 sequence to mediate the self-association of NPAT. Mechanistically, the anchoring of KPNA3 to the NPAT-NLS sterically blocks C-SIF motif-dependent NPAT self-association. This leads to the suppression of aberrant NPAT condensation in the cytoplasm. Collectively, our study reveals a previously unappreciated role of KPNA3 in modulating HLB formation and delineates a steric hindrance mechanism that prevents inappropriate cytoplasmic NPAT condensation.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11613458/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142769240","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Painting lysosomes to study organelle heterogeneity. 绘制溶酶体以研究细胞器的异质性。

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2025-01-06 Epub Date: 2024-12-16 DOI: 10.1083/jcb.202412011

Di Chen, Maximiliano G Gutierrez

引用次数: 0

Nap1 and Kap114 co-chaperone H2A-H2B and facilitate targeted histone release in the nucleus. Nap1 和 Kap114 共同合成 H2A-H2B，促进组蛋白在细胞核中的定向释放。

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2025-01-06 Epub Date: 2024-11-27 DOI: 10.1083/jcb.202408193

Ho Yee Joyce Fung, Jenny Jiou, Ashley B Niesman, Natalia E Bernardes, Yuh Min Chook

{"title":"Nap1 and Kap114 co-chaperone H2A-H2B and facilitate targeted histone release in the nucleus.","authors":"Ho Yee Joyce Fung, Jenny Jiou, Ashley B Niesman, Natalia E Bernardes, Yuh Min Chook","doi":"10.1083/jcb.202408193","DOIUrl":"10.1083/jcb.202408193","url":null,"abstract":"Core histones, synthesized and processed in the cytoplasm, must be chaperoned as they are transported into the nucleus for nucleosome assembly. The importin Kap114 transports H2A-H2B into the yeast nucleus, where RanGTP facilitates histone release. Kap114 and H2A-H2B also bind the histone chaperone Nap1, but how Nap1 and Kap114 cooperate in transport and nucleosome assembly remains unclear. Here, biochemical and structural analyses show that Kap114, H2A-H2B, and a Nap1 dimer (Nap12) associate in the absence and presence of RanGTP to form equimolar complexes. A previous study had shown that RanGTP reduces Kap114's ability to chaperone H2A-H2B, but a new cryo-EM structure of the Nap12•H2A-H2B•Kap114•RanGTP complex explains how both Kap114 and Nap12 interact with H2A-H2B, restoring its chaperoning within the assembly while effectively depositing it into nucleosomes. Together, our results suggest that Kap114 and Nap12 provide a sheltered path that facilitates the transfer of H2A-H2B from Kap114 to Nap12, ultimately directing its specific deposition into nucleosomes.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11602657/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142728953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Arrayed CRISPRi library to suppress genes required for Schizosaccharomyces pombe viability. 通过 CRISPRi 文库阵列抑制小鼠酵母生存所需的基因。

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2025-01-06 Epub Date: 2024-10-08 DOI: 10.1083/jcb.202404085

Ken Ishikawa, Saeko Soejima, Takashi Nishimura, Shigeaki Saitoh

{"title":"Arrayed CRISPRi library to suppress genes required for Schizosaccharomyces pombe viability.","authors":"Ken Ishikawa, Saeko Soejima, Takashi Nishimura, Shigeaki Saitoh","doi":"10.1083/jcb.202404085","DOIUrl":"10.1083/jcb.202404085","url":null,"abstract":"The fission yeast, Schizosaccharomyces pombe, is an excellent eukaryote model organism for studying essential biological processes. Its genome contains ∼1,200 genes essential for cell viability, most of which are evolutionarily conserved. To study these essential genes, resources enabling conditional perturbation of target genes are required. Here, we constructed comprehensive arrayed libraries of plasmids and strains to knock down essential genes in S. pombe using dCas9-mediated CRISPRi. These libraries cover ∼98% of all essential genes in fission yeast. We estimate that in ∼60% of these strains, transcription of a target gene was repressed so efficiently that cell proliferation was significantly inhibited. To demonstrate the usefulness of these libraries, we performed metabolic analyses with knockdown strains and revealed flexible interaction among metabolic pathways. Libraries established in this study enable comprehensive functional analyses of essential genes in S. pombe and will facilitate the understanding of essential biological processes in eukaryotes.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11465072/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142390748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

SARS-CoV-2 specific adaptations in N protein inhibit NF-κB activation and alter pathogenesis. N 蛋白中的 SARS-CoV-2 特异适应性可抑制 NF-κB 激活并改变发病机制。

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2025-01-06 Epub Date: 2024-12-16 DOI: 10.1083/jcb.202404131

Xiao Guo, Shimin Yang, Zeng Cai, Shunhua Zhu, Hongyun Wang, Qianyun Liu, Zhen Zhang, Jiangpeng Feng, Xianying Chen, Yingjian Li, Jikai Deng, Jiejie Liu, Jiali Li, Xue Tan, Zhiying Fu, Ke Xu, Li Zhou, Yu Chen

{"title":"SARS-CoV-2 specific adaptations in N protein inhibit NF-κB activation and alter pathogenesis.","authors":"Xiao Guo, Shimin Yang, Zeng Cai, Shunhua Zhu, Hongyun Wang, Qianyun Liu, Zhen Zhang, Jiangpeng Feng, Xianying Chen, Yingjian Li, Jikai Deng, Jiejie Liu, Jiali Li, Xue Tan, Zhiying Fu, Ke Xu, Li Zhou, Yu Chen","doi":"10.1083/jcb.202404131","DOIUrl":"https://doi.org/10.1083/jcb.202404131","url":null,"abstract":"Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and severe acute respiratory syndrome coronavirus (SARS-CoV) exhibit differences in their inflammatory responses and pulmonary damage, yet the specific mechanisms remain unclear. Here, we discovered that the SARS-CoV-2 nucleocapsid (N) protein inhibits the activation of the nuclear factor-κB (NF-κB) pathway and downstream signal transduction by impeding the assembly of the transforming growth factor β-activated kinase1 (TAK1)-TAK1 binding protein 2/3 (TAB2/3) complex. In contrast, the SARS-CoV N protein does not impact the NF-κB pathway. By comparing the amino acid sequences of the SARS-CoV-2 and SARS-CoV N proteins, we identified Glu-290 and Gln-349 as critical residues in the C-terminal domain (CTD) of the SARS-CoV-2 N protein, essential for its antagonistic function. These findings were further validated in a SARS-CoV-2 trans-complementation system using cellular and animal models. Our results reveal the distinctions in inflammatory responses triggered by SARS-CoV-2 and SARS-CoV, highlighting the significance of specific amino acid alterations in influencing viral pathogenicity.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142828625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Kinetochores grip microtubules with directionally asymmetric strength. 动芯以方向不对称的力量抓住微管。

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2025-01-06 Epub Date: 2024-11-01 DOI: 10.1083/jcb.202405176

Joshua D Larson, Natalie A Heitkamp, Lucas E Murray, Andrew R Popchock, Sue Biggins, Charles L Asbury

{"title":"Kinetochores grip microtubules with directionally asymmetric strength.","authors":"Joshua D Larson, Natalie A Heitkamp, Lucas E Murray, Andrew R Popchock, Sue Biggins, Charles L Asbury","doi":"10.1083/jcb.202405176","DOIUrl":"10.1083/jcb.202405176","url":null,"abstract":"For accurate mitosis, all chromosomes must achieve \"biorientation,\" with replicated sister chromatids coupled via kinetochores to the plus ends of opposing microtubules. However, kinetochores first bind the sides of microtubules and subsequently find plus ends through a trial-and-error process; accurate biorientation depends on the selective release of erroneous attachments. Proposed mechanisms for error-correction have focused mainly on plus-end attachments. Whether erroneous side attachments are distinguished from correct side attachments is unknown. Here, we show that side-attached kinetochores are very sensitive to microtubule polarity, gripping sixfold more strongly when pulled toward plus versus minus ends. This directionally asymmetric grip is conserved in human and yeast subcomplexes, and it correlates with changes in the axial arrangement of subcomplexes within the kinetochore, suggesting that internal architecture dictates attachment strength. We propose that the kinetochore's directional grip promotes accuracy during early mitosis by stabilizing correct attachments even before both sisters have found plus ends.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11533501/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142557910","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

ER export via SURF4 uses diverse mechanisms of both client and coat engagement. 通过 SURF4 输出的 ER 采用了客户和外衣参与的多种机制。

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2025-01-06 Epub Date: 2024-11-12 DOI: 10.1083/jcb.202406103

Julija Maldutyte, Xiao-Han Li, Natalia Gomez-Navarro, Evan G Robertson, Elizabeth A Miller

引用次数: 0

Unveiling the cell biology of hippocampal neurons with dendritic axon origin. 揭示具有树突轴突起源的海马神经元的细胞生物学。

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2025-01-06 Epub Date: 2024-11-04 DOI: 10.1083/jcb.202403141

Yuhao Han, Daniela Hacker, Bronte Catharina Donders, Christopher Parperis, Roland Thuenauer, Christophe Leterrier, Kay Grünewald, Marina Mikhaylova

{"title":"Unveiling the cell biology of hippocampal neurons with dendritic axon origin.","authors":"Yuhao Han, Daniela Hacker, Bronte Catharina Donders, Christopher Parperis, Roland Thuenauer, Christophe Leterrier, Kay Grünewald, Marina Mikhaylova","doi":"10.1083/jcb.202403141","DOIUrl":"10.1083/jcb.202403141","url":null,"abstract":"In mammalian axon-carrying-dendrite (AcD) neurons, the axon emanates from a basal dendrite, instead of the soma, to create a privileged route for action potential generation at the axon initial segment (AIS). However, it is unclear how such unusual morphology is established and whether the structure and function of the AIS in AcD neurons are preserved. By using dissociated hippocampal cultures as a model, we show that the development of AcD morphology can occur prior to synaptogenesis and independently of the in vivo environment. A single precursor neurite first gives rise to the axon and then to the AcD. The AIS possesses a similar cytoskeletal architecture as the soma-derived AIS and similarly functions as a trafficking barrier to retain axon-specific molecular composition. However, it does not undergo homeostatic plasticity, contains lesser cisternal organelles, and receives fewer inhibitory inputs. Our findings reveal insights into AcD neuron biology and underscore AIS structural differences based on axon onset.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11536041/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142568695","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Ca2+ tunneling architecture and function are important for secretion. Ca2+ 隧道结构和功能对分泌非常重要。

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2025-01-06 Epub Date: 2024-11-05 DOI: 10.1083/jcb.202402107

Raphael J Courjaret, Larry E Wagner, Rahaf R Ammouri, David I Yule, Khaled Machaca

引用次数: 0

Heterogeneity of late endosome/lysosomes shown by multiplexed DNA-PAINT imaging. 多重 DNA-PAINT 成像显示晚期内膜体/溶酶体的异质性。

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2025-01-06 Epub Date: 2024-11-01 DOI: 10.1083/jcb.202403116

Charles Bond, Siewert Hugelier, Jiazheng Xing, Elena M Sorokina, Melike Lakadamyali

{"title":"Heterogeneity of late endosome/lysosomes shown by multiplexed DNA-PAINT imaging.","authors":"Charles Bond, Siewert Hugelier, Jiazheng Xing, Elena M Sorokina, Melike Lakadamyali","doi":"10.1083/jcb.202403116","DOIUrl":"10.1083/jcb.202403116","url":null,"abstract":"Late endosomes/lysosomes (LELs) are crucial for numerous physiological processes and their dysfunction is linked to many diseases. Proteomic analyses have identified hundreds of LEL proteins; however, whether these proteins are uniformly present on each LEL, or if there are cell-type-dependent LEL subpopulations with unique protein compositions is unclear. We employed quantitative, multiplexed DNA-PAINT super-resolution imaging to examine the distribution of seven key LEL proteins (LAMP1, LAMP2, CD63, Cathepsin D, TMEM192, NPC1, and LAMTOR4). While LAMP1, LAMP2, and Cathepsin D were abundant across LELs, marking a common population, most analyzed proteins were associated with specific LEL subpopulations. Our multiplexed imaging approach identified up to eight different LEL subpopulations based on their unique membrane protein composition. Additionally, our analysis of the spatial relationships between these subpopulations and mitochondria revealed a cell-type-specific tendency for NPC1-positive LELs to be closely positioned to mitochondria. Our approach will be broadly applicable to determining organelle heterogeneity with single organelle resolution in many biological contexts.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"224 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11533445/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142557909","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0